Structural evidence for a new binding mode for guanine bases: Implications for the binding of dinuclear anti-tumor agents to DNA
- Michigan State Univ., East Lansing, MI (United States)
- Indiana Univ., Bloomington, IN (United States)
A central theme in bioorganic chemistry is the investigation of transition metal anti-tumor compounds, particularly those of the platinum group elements. Certain dinuclear metal complexes are known to exhibit carcinostatic activity, but unlike cis-platin, the mechanism of action is not well understood. Previous binding studies of Rh{sub 2}(O{sub 2}CCH{sub 3}){sub 4} with various nucleosides and nucleotides led to claims that only adenine bases are capable of forming complexes. This paper presents evidence from model studies with 9-ethylguanine, guanosine and the dinucleotides d(GpGp) and d(GpG) that support an alternative binding mode for dinuclear complexes with DNA base. Reactions of Rh{sub 2}(O{sub 2}CR{sub 3}){sub 4} and [Ru{sub 2}(O{sub 2}CR{sub 3}{sub 4}{sup +} with guanosine and 9-ethylguanine support the formation of novel products of general formula [M{sub 2}(O{sub 2}CR{sub 3}){sub 2}(purine){sub 2}]{sup 2+}]. An x-ray structure of [Rh{sub 2}(O{sub 2}CCF{sub 3}){sub 2}(9-ethyl-guanine)){sub 2}]{sup 2+} revealed an unprecendented bridging N7-06 interaction for 9-ethylguanine in the complex. In related studies, Rh{sub 2}(O{sub 2}CCF{sub 3}){sub 4} undergoes facile complex formation with d(GpGp) and d(GpG) to yield products whose properties closely resemble those of the purine and nucleoside compounds. Results of molecular mechanics calculations, {sup 1}H NMR and electronic spectroscopies, fast atom bombardment mass spectrometry (FAB-MS) and crystallography are presented to support these conclusions.
- OSTI ID:
- 141101
- Report Number(s):
- CONF-930304-; TRN: 93:003688-0776
- Resource Relation:
- Conference: 205. American Chemical Society national meeting, Denver, CO (United States), 28 Mar - 2 Apr 1993; Other Information: PBD: 1993; Related Information: Is Part Of 205th ACS national meeting; PB: 1951 p.
- Country of Publication:
- United States
- Language:
- English
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